Rational evolution of cytokines for higher stability, the cytokines and encoding nucleic acid molecules
First Claim
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1. A modified granulocyte-macrophage colony-stimulating factor (GM-CSF) cytokine, comprising one or more amino acid replacements in its sequence of amino acid residues, wherein:
- the modified GM-CSF cytokine exhibits increased resistance to proteolysis by a serum protease or a protease of the digestive tract compared to the unmodified GM-CSF cytokine that does not comprise the one or more amino acid replacements.
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Abstract
Compositions of modified cytokines and uses thereof generated using processes and systems for the high throughput directed evolution of peptides and proteins, particularly cytokines that act in complex biological settings, are provided. Also provided are modified cytokines formulated for oral delivery and uses thereof to treat diseases and conditions mediated by cytokines.
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Citations
51 Claims
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1. A modified granulocyte-macrophage colony-stimulating factor (GM-CSF) cytokine, comprising one or more amino acid replacements in its sequence of amino acid residues, wherein:
the modified GM-CSF cytokine exhibits increased resistance to proteolysis by a serum protease or a protease of the digestive tract compared to the unmodified GM-CSF cytokine that does not comprise the one or more amino acid replacements. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 45, 46, 47, 48)
- 32. A pharmaceutical composition formulated for oral administration, comprising a GM-CSF cytokine that contains one or more amino acid modification(s), whereby the GM-CSF cytokine exhibits increased protease resistance compared to a GM-CSF cytokine that does not contain the modification(s).
Specification